P373: UPDATES FROM A PHASE II TRIAL OF MINI-HYPER-CVD-INOTUZUMAB WITH OR WITHOUT BLINATUMOMAB IN OLDER PATIENTS WITH NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME (PH)-NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Fadi Haddad, Elias Jabbour, Cedric Nasnas, Nicholas Short, Lewis Nasr, Walid Macaron, Marianne Zoghbi, Farhad Ravandi, Nitin Jain, Tapan Kadia, Naval Daver, Gautam Borthakur, Courtney Dinardo, Jovitta Jacob, Edith Roy, Christopher Loiselle, Anna Milton, Juan Rivera, Rebecca Garris, Hagop Kantarjian
Journal: HemaSphere (2023)

Background: The overall survival (OS) of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) has significantly improved with the introduction of targeted therapies, inotuzumab ozogamicin and blinatumomab. Combining these agents with low-dose chemotherapy in the frontline setting might improve outcomes. Aims: The aim of this analysis is to evaluate the combination of low-intensity chemotherapy mini-Hyper-CVD and inotuzumab ozogamicin, with or without blinatumomab, in older patients with newly diagnosed Ph-negative B-cell ALL. Methods: Adults ≥60 years with newly diagnosed Ph-negative B-cell ALL received mini-Hyper-CVD (mini-HCVD) for up to 8 cycles. Initially, inotuzumab ozogamicin was given at 1.3-1.8mg/m2 on Day 3 of Cycle 1 and 0.8-1.3mg/m2 on Day 3 of Cycles 2-4. Rituximab (if CD20+) and prophylactic intrathecal chemotherapy were given for the first 4 cycles. Responders received POMP maintenance for up to 3 years. Beginning with patient #50, inotuzumab ozogamicin was given in fractionated doses each cycle (0.6 mg/m2 on Day 2 and 0.3 mg/m2 on Day 8 of Cycle 1; 0.3 mg/m2 on Day 2 and 8 of Cycle 2-4) and 4 cycles of blinatumomab were given following 4 cycles of mini-HCVD plus inotuzumab. Maintenance was with 12 cycles of POMP and 4 cycles of blinatumomab (1 cycle of blinatumomab after 3 cycles of POMP). Results: 83 patients were treated, of whom 6 were in complete remission (CR) at enrollment (Figure 1). Among 77 evaluable pts, 76 (99%) responded (CR, 90%). Among responders, the rates of MRD negativity by flow cytometry were 79% and 94% after Cycle 1 and overall, respectively. No early death was observed. Among 82 pts in remission, 11 (13%) relapsed, 4 (5%) underwent ASCT, 34 (41%) remain in ongoing continuous remission, 33 (41%) died in remission, of whom 9 died after developing MDS/AML. Three patients (4%) developed veno-occlusive disease (VOD), 2 after subsequent ASCT. After a median follow-up of 65 months (range, 6-126), the 5-year continuous remission duration and OS rates were 78% and 48%, respectively. Age ≥70 and adverse cytogenetics were associated with worse outcomes. The inferior outcome in pts ≥70 yrs was primarily attributed to higher rates of death in CR. The 5-year OS for patients age 60-69 years without adverse cytogenetics (n=40), age 60-69 with adverse cytogenetics (n=15), age ≥70 without adverse cytogenetics (n=24) and age ≥70 with adverse cytogenetics (n=4) were 72%, 27%, 38% and 0%, respectively. Summary/Conclusion: Favorable outcomes were observed in older patients with newly diagnosed Ph-negative ALL treated with mini-HCVD plus inotuzumab ozogamicin, with or without blinatumomab, with a 5-year OS of 48%. This regimen was well tolerated, with a low incidence of VOD and no early death observed.Keywords: Philadelphia chromosome, Phase II, Acute lymphoblastic leukemia